Elucidation of activation mechanism of the lectin complement pathway

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Mannose-binding lectin (MBL, also called MBP) is associated with two types of serine protease, MASP-1 and MASP-2, which are structually homologous. Upon binding to carbohydrates such as mannose on pathogens, the MBL-MASP complex activates the lectin complement pathway. The aim of this research was to elucidate the activation mechamism of the lectin pathway. We obtained the following results.1) A 22kDa protein (sMAP) is present in an MBL-MASP preparation and is associated with MASP-1. cDNA analysis of sMAP revealed that sMAP is derived from the MASP-2 gene by alternative polyadenylation.2) We developed an ELISA for MASP-1 levels in human serum and found that MBL and MASP-1 levels in serum are not correlated in the individual, and that MASP-1 exists as MBL-bound and MBL-unbound forms, the latter of which is associated with sMAP in part.3) MASP-1 and MASP-2 exhibit proteolytic activities towards C3 and C4, respectively.4) MBL exists as a homopolymer with various sizes. Analysis of one of MBL homopolymers revealed that it copurified with MASP-1 and sMAP but not with MASP-2.